Mechanisms of Mycobacterial-Induced Immunity in HIV-Infected and/or Uninfected Individuals to Inform Innovative Tuberculosis Vaccine Design (R01 Clinical Trial Not Allowed) | PAR 19 307

Opportunity Information: Apply for PAR 19 307

The NIH grant opportunity PAR-19-307 is an R01 funding announcement that supports research aimed at pinpointing and explaining the immune responses that actually protect people from Mycobacterium tuberculosis (Mtb) infection or from progressing to active tuberculosis (TB) disease after exposure or infection. The central theme is mechanism: applicants are expected to move beyond cataloging immune markers or reporting associations and instead generate evidence that clarifies how specific immune responses work, where and when they occur, and how they influence real disease outcomes. The ultimate goal is to produce knowledge that can be directly used to design or improve next-generation TB vaccines, including vaccines intended to work well in people living with HIV.

This FOA emphasizes protective immunity across multiple real-world contexts. Proposed studies can focus on immune responses that arise during natural mycobacterial infection, after vaccination with Bacillus Calmette-Guerin (BCG), or following receipt of investigational TB vaccines. It also allows work at any stage of infection, which could include early exposure, latent infection, incipient disease, or active TB, as long as the research is aimed at identifying immunological mechanisms that determine protection versus progression. A notable feature is that studies may include HIV-infected individuals, HIV-uninfected individuals, or both, reflecting the major role HIV plays in TB susceptibility and the need for vaccines that perform in settings where HIV is prevalent.

A key scientific expectation is that applications will characterize immune responses in a way that integrates timing, anatomical location, and functional contribution to outcomes. In practice, this means the NIH is looking for projects that can tell a coherent story about how mucosal immunity (for example, immune activity in the respiratory tract where Mtb first establishes infection) and/or systemic immunity (blood and broader immune compartments) develops over time and influences whether someone resists infection, controls bacterial growth, maintains latency, or progresses to symptomatic disease. The FOA highlights mucosal and systemic responses specifically, signaling interest in studies that do not rely only on peripheral blood measurements if the biological question is rooted in lung or airway immunity, while still allowing systemic analyses when appropriate.

The announcement also makes clear what it does not want: purely descriptive work that stays within what is already generally known about Mtb infection, immune responses to TB vaccines, or immune modulation caused by non-tuberculous mycobacterial (NTM) exposure and HIV/AIDS. NTM exposure and HIV are still very relevant under this FOA, but they are framed as variables that shape immunity and vaccine performance and should be addressed with deeper mechanistic insight rather than surface-level profiling. Competitive projects would therefore be expected to propose strategies that can distinguish correlates from causes, explain why certain immune signatures appear, and demonstrate how those responses might be harnessed or induced by vaccination to provide durable protection.

Administratively, this is a discretionary NIH grant using the R01 mechanism, and the title specifies "Clinical Trial Not Allowed," meaning applicants should not propose a clinical trial as defined by NIH rules. Studies can still involve human participants and clinical specimens, but the work must be structured as mechanistic research rather than an interventional trial testing clinical outcomes. The funding activity category is health, and the CFDA number listed is 93.855. The opportunity was created on June 28, 2019, and the original closing date shown is September 10, 2020, which is important for historical context and for anyone checking whether the FOA is still active or has been reissued in an updated form.

Eligibility is broad and includes many types of applicants: state, county, and local governments; public and private institutions of higher education; independent school districts; special district governments; federally recognized Native American tribal governments as well as other tribal organizations; public housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and other eligible entities. The FOA also explicitly calls out additional eligible applicants such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American and Native American Pacific Islander-Serving Institutions (AANAPISIs), faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, and non-U.S. entities (foreign organizations) and regional organizations. This breadth aligns with the global burden of TB and HIV and supports collaborations that can access relevant cohorts, clinical settings, and pathogen diversity.

Taken together, PAR-19-307 is designed to fund rigorous, hypothesis-driven immunology that clarifies what protective anti-mycobacterial immunity looks like, how it is generated, and how it is altered by factors like HIV and environmental mycobacteria. The practical deliverable the NIH is pushing for is actionable vaccine-relevant insight: a clearer map of immune mechanisms that can guide antigen selection, adjuvant and platform decisions, routes of immunization (including those that target mucosal sites), and strategies tailored to populations at highest risk, including people living with HIV.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Mechanisms of Mycobacterial-Induced Immunity in HIV-Infected and/or Uninfected Individuals to Inform Innovative Tuberculosis Vaccine Design (R01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855.
• This funding opportunity was created on 2019-06-28.
• Applicants must submit their applications by 2020-09-10. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 19 307

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